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Neurodegenerative diseases—like amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), Alzheimer’s, and Parkinson’s—are complicated, chronic ailments that can present with a variety of symptoms, worsen at different rates, and have many underlying genetic and environmental causes, some of which are unknown. ALS, in particular, affects voluntary muscle movement and is always fatal, but while most people survive for only a few years after diagnosis, others live with the disease for decades. Manifestations of ALS can also vary significantly; often slower disease development correlates with onset in the limbs and affecting fine motor skills, while the more serious, bulbar ALS impacts swallowing, speaking, breathing, and mobility. Therefore, understanding the progression of diseases like ALS is critical to enrollment in clinical trials, analysis of potential interventions, and discovery of root causes.

However, assessing disease evolution is far from straightforward. Current clinical studies typically assume that health declines on a downward linear trajectory on a symptom rating scale, and use these linear models to evaluate whether drugs are slowing disease progression. However, data indicate that ALS often follows nonlinear trajectories, with periods where symptoms are stable alternating with periods when they are rapidly changing. Since data can be sparse, and health assessments often rely on subjective rating metrics measured at uneven time intervals, comparisons across patient populations are difficult. These heterogenous data and progression, in turn, complicate analyses of invention effectiveness and potentially mask disease origin.

Continue reading “Machine-learning method shows neurodegenerative disease can progress in newly identified patterns” »

Additionally, epigenetic changes were suggested to be a possible link [30, 31] between adverse childhood experiences and mortality as well as higher morbidity burden in late life [32]. It was proposed that this link could be mediated by health-adverse coping mechanisms (activated as a result of high levels of anxiety and depression) that are associated with adverse childhood experiences [33]. Some of these coping strategies, such as smoking, alcohol abuse and and a high BMI resulting from unhealthy eating habits, were shown to be associated with DNAmAA in some studies [34,35,36]. However, these results were not unequivocally replicated [37,38,39] (reviewed in ref. [40]).

Previous studies that examined the relationship between DNAmAA and stress operationalized stress as low socioeconomic status (SES) [41, 42], (childhood) trauma [26, 43,44,45], racial discrimination [46], or exposure to violence [47]. Many previous studies on the topic focused on changes in DNAm age during childhood as this period is known to be particularly prone to stress-related epigenetic changes [29].

In contrast, in this work we focus on older age which was shown to be the second most vulnerable phase in a person’s life in terms of epigenetics [29]. As epigenetic modifications remain even after the psychological stimulus has ceased there is the possibility of cumulating effects on the epigenome exerted by repeated psychological stressors [29]. Specifically, we analyzed the association between the amount of experienced stress (measured by Cohen’s Perceived Stress Scale [PSS] [48]) and several DNAm age estimators (i.e. the 7-CpG clock [49], Horvath’s clock [50], Hannum’s clock [51], PhenoAge [34], GrimAge [52]) in 1,100 older adults. While the PSS represents a well-established marker of perceived stress [48], to our knowledge it has not been investigated in the context of epigenetic aging before. While we were able to replicate well-established associations with perceived stress, none of the five epigenetic clocks analyzed in the current study were associated with the perception of stress.

So one treated rat made it to 45 months which is 113 for people. A 2nd trial is underway to try and increase these results. Also, the human topical test for E5 is just for skin rejuvenation, not fro full rejuvenation or lifespan increase for people.

In this video we report on the August 2022 update from Dr. Katcher’s experiment with E5 along with some other details about the book launch in other languages, the new experiment and topical E5 for humans!

Continue reading “Dr Katcher’s E5 Experiment September 2022 Update | Review” »

All eyes are on the Emerald Isle this week as the Longevity Summit Dublin brings together a host of speakers covering the spectrum of this booming sector. Delegates have been hearing from some of the leading entrepreneurs, companies, investors, and researchers in the field as they address many of the hot-button topics affecting longevity. One of those speakers is the so-called “father of genomics” – Harvard professor of genetics, George Church – who closes the conference later today with a keynote on Gene, cell and organ therapies for de-aging.

Longevity. Technology: In addition to his Harvard professorship, Church heads up synthetic biology at the Wyss Institute, where he oversees development of new tools with applications in regenerative medicine. Much of his focus more recently has been on the development of gene therapies targeting age-related disease, a passion that led him to co-found Rejuvenate Bio, with the goal of creating “full age reversal gene therapies.” We caught up with Church ahead of his Dublin presentation for a brief conversation on longevity.

Dr Church’s name is synonymous with genomic science, and he was a key contributor to the Human Genome Project and technologies including next-generation fluorescent and nanopore sequencing, aimed at understanding genetic contributions to human disease. However, he doesn’t feel that those initiatives did a huge amount to move the aging field forward.

Scientist from the National University of Singapore (NUS) have found a novel way of growing cell-based meat by zapping animal cells with a magnet. This new technique simplifies the production process of cell-based meat by reducing reliance on animal products, and it is also greener, cleaner, safer and more cost-effective.

Cultured meat is an alternative to animal farming with advantages such as reducing carbon footprint and the risk of transmitting diseases in animals. However, the current method of producing cultured meat involves using other animal products, which largely defeats the purpose, or drugs to stimulate the growth of the meat.

To cultivate cell-based meat, animal cells are fed animal serum—usually fetal bovine serum (FBS), which is a mixture harvested from the blood of fetuses excised from pregnant cows slaughtered in the dairy or meat industries—to help them grow and proliferate. This is a critical, yet cruel and expensive, step in the current cell-based meat production process. Ironically, many of these molecules come from the muscles within the slaughtered animal, but scientists did not know how to stimulate their release in production scale bioreactors. Other methods to promote cell growth are using drugs or relying on genetic engineering.

For the first time, scientists will be able to test therapeutics for a group of rare neurodegenerative diseases that affect infants and young children, thanks to a new research model created by scientists at the University of Wisconsin-Madison. Their results are published in the Proceedings of the National Academy of Sciences.

Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative diseases caused by genetic mutations. They lead tens of thousands of children to develop increased muscle tone in their lower extremities, causing weakness in their legs and ultimately affecting their ability to crawl or walk.

“Kids as early as six months of age that have these mutations start to show signs of disease,” says Anjon Audhya, a professor in the Department of Biomolecular Chemistry at UW-Madison. “Between two and five years of age, these kids become wheelchair-bound, and they unfortunately will never be able to walk.”

Ideally, the nanopore dimensions should be comparable to those of the analyte for the presence of the analyte to produce a measurable change in the ionic current amplitude above the noise level. Nanopores can be formed in several ways, with a wide range of pore diameters. Biological nanopores are formed by the self-assembly of either protein subunits, peptides or even DNA scaffolds in lipid bilayers or block copolymer membranes^1,3,6,17,18. They possess atomically precise dimensions controlled by biopolymer sequences, providing the ability to recognize biomolecules with constriction diameters of ~1–10 nm. Solid-state nanopores are crafted in thin inorganic or plastic membranes (for example, SiN_x), which allows the nanopores to have extended diameters of up to hundreds of nanometres, permitting the entry or analysis of large biomolecules and complexes. The tools for fabricating solid-state nanopores, which include electron/ion milling^4,5, laser-based optical etching^19,20 and the dielectric breakdown of ultrathin solid membranes^21,22, can be used to manipulate nanopore size at the nanometre scale, but allow only limited control over the surface structure at the atomic level in contrast to biological nanopores. The chemical modification and genetic engineering of biological nanopores, or the introduction of biomolecules to functionalize solid-state nanopores²³, can further enhance the interactions between a nanopore and analytes, improving the overall sensitivity and selectivity of the device^{2,17,24,25,26}. This feature allows nanopores to controllably capture, identify and transport a wide variety of molecules and ions from bulk solution.

Nanopore technology was initially developed for the practicable stochastic sensing of ions and small molecules^2,27,28. Subsequently, many developmental efforts were focused on DNA sequencing^1,7,8,9. Now, however, nanopore applications extend well beyond sequencing, as the methodology has been adapted to analyse molecular heterogeneities and stochastic processes in many different biochemical systems (Fig. 1). First, a key advantage of nanopores lies in their ability to successively capture many single molecules one after the other at a relatively high rate, which allows nanopores to explore large populations of molecules at the single-molecule level in reasonable timeframes. Second, nanopores essentially convert the structural and chemical properties of the analytes into a measurable ionic current signal, even achieving enantiomer discrimination²⁹. The technology can be used to report on multiple molecular features while circumventing the need for labelling chemistries, which may complicate the overall analysis process and affect the molecular structures. For example, nanopores can discriminate nearly 13 different amino acids in a label-free manner, including some with minute structural differences³⁰. An important aspect is the ability of nanopores to identify species³¹ that lack suitable labels for signal amplification or whose information is hidden in the noise of analytical devices. Consequently, nanopores may serve well in molecular diagnostic applications required for precision medicine, which achieves the identification of nucleic acid, protein or metabolite analytes and other biomarkers^{11,32,33,34,35}. Third, nanopores provide a well-defined scaffold for controllably designing and constructing biomimetic systems, which involve a complex network of biomolecular interactions. These nanopore systems track the binding dynamics of transported biomolecules as they interact with nanopore surfaces, hence serving as a platform for unravelling complex biological processes (for example, the transport properties of nuclear pore complexes)^36,37,38,39. Fourth, chemical groups can be spatially aligned within a protein nanopore, providing a confined chemical environment for site-selective or regioselective covalent chemistry. This strategy has been used to engineer protein nanoreactors to monitor bond-breaking and bond-making events^40,41.

Here we discuss the latest advances in nanopore technologies beyond DNA sequencing and the future trajectory of the field, as well as the opportunities and main challenges for the next decade. We specifically address the emerging nanopore methods for protein analysis and protein sequencing, single-molecule covalent chemistry, single-molecule analysis of clinical samples and insights into the use of biomimetic pores for analysing complex biological processes.

Organs are in short supply. About 17 people die each day waiting for a transplant. New experimental methods of growing and tweaking organs could help.

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Continue reading “Resting Heart Rate And Heart Rate Variability: What’s Optimal, 1,502 Days of Data” »